P1094: CHARACTERISTICS, MANAGEMENT, AND OUTCOMES OF PATIENTS WITH T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA AT A LARGE TERTIARY CARE CENTER
Authors: H. Audil, M. Shah, K. Rabe, W. Ding, P. Hampel, N. N. Bennani, T. Call, C. Hanson, Y. Wang, A. Koehler, S. Schwager, J. Leis, S. Slager, S. Kenderian, A. Al-Kali, G. Nowakowski, M. Shi, S. Parikh
Journal: HemaSphere (2022)

Background: Large granular lymphocytic leukemia (LGLL) comprises 2-6% of chronic lymphoproliferative disorders. T-LGLL accounts for approximately 85% of cases, while NK-LGLL represents 15% of cases. There is a significant knowledge gap regarding diagnosis, management, and outcomes of LGLL. Aims: Our aims were to describe the clinical characteristics, time to first therapy (TTFT), type of first line therapy, response to treatment, and overall survival (OS) in patients with LGLL seen at our institution. Methods: We identified LGLL patients from the Mayo Clinic Chronic Lymphoproliferative Disorders Database seen between 1/1995-7/2021. At least 3 of the following 4 criteria were used to diagnose LGLL (T-LGLL or NK-LGLL): (1) a distinct T-cell or NK-cell population by flow cytometry; (2) a clonal T-cell or NK-cell population; (3) intrasinusoidal cytotoxic T-cell or NK-cell infiltrates in bone marrow, spleen, or liver; and (4) persistence of the abnormal T-cell or NK-cell population or unexplained cytopenia for more than 6 months (Salama, BCJ, 2022). Baseline clinical characteristics, TTFT, first line therapies, and OS were analyzed for all patients. The Mayo Clinic IRB approved this study. Results: We identified 217 patients who met inclusion criteria for LGLL diagnosis; 196 (90.3%) patients had T-LGLL and 21 (9.7%) patients had NK-LGLL. The median age at diagnosis was 65 years [range 21-86], and 120 (55.3%) were male. 159 (73.3%) patients had evidence of cytopenia at the time of diagnosis. Frequently associated clinical characteristics included dependence on red cell or platelet transfusions (44.3%), colony-stimulating factors (20.0%), or both (21.7%); splenomegaly (32.9%); history of autoimmune disease (24.9%); history of hematologic disorder (18.4%) or malignancy (5.6%); and constitutional symptoms (11.1%). The median follow-up was 8.4 years; 133 patients died, and 111 patients were treated for LGLL during this period. The median TTFT after diagnosis was 47.0 months (42.8 for T-LGLL and 68.0 for NK-LGLL) with a median of 1 (range 0-11) line of treatment. First-line therapy consisted of methotrexate in 33 (29.7%) patients, cyclophosphamide in 25 (22.5%), cyclosporine in 6 (5.4%), chlorambucil in 6 (5.4%), rituximab in 5 (4.5%), steroids alone in 17 (15.3%), and splenectomy in 7 (6.3%); 5 (4.5%) patients received combination therapy and 2 (1.8%) received IVIG. Alemtuzumab, cladribine, fludarabine, lenalidomide, and vincristine were first-line therapy in 1 (0.9%) patient each. Response to first-line therapy (Lamy, Blood, 2011) consisted of complete response (CR) in 31%, partial response (PR) in 33%, and treatment failure or progressive disease in 36% patients. The median OS was 11.0 years: 11.0 years for T-LGLL and 8.1 years for NK-LGLL (p = 0.90; Figure 1). Image:Summary/Conclusion: In this retrospective study of LGLL, we utilized stringent pathology inclusion criteria to allow for analyses of a homogenous cohort of patients seen at our institution. One in 4 patients with LGLL had a concomitant autoimmune condition, and 25% had a concomitant hematologic condition or hematologic malignancy at the time of initial diagnosis. Approximately a third of all patients who needed LGLL treatment did not achieve a response to frontline therapy, suggesting that newer treatments are needed to improve outcomes of this rare disease.